Continuous wave and FT NMR spectra have been obtained of nuclease. Paramagnetic ions (such as Gd (III), have been used as perturbants of the NMR resonances. This approach has allowed the accurate measurement of distances within the protein and between the protein and a substance analog, pdTp. These distances have been used, with a computer modeling program, to generate a solution geometry for nuclease and its substrate analog. The geometry established for the protein in solution is very similar to that in the crystal structure, with the exception of the location of the methyl group on the substrate analog. The reasons for this discrepancy are not clear. Data for several other substrate analogs and several substrates have been collected for similar analyses.